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Journal Article

Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons77703

Bange,  J.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77854

Cheburkin,  Y.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;
Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78237

Knyazeva,  T.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77985

Gärtner,  S.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78774

Sures,  I.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78233

Knayzev,  P.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78812

Ullrich,  A.
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Bange, J., Prechtl, D., Cheburkin, Y., Specht, K., Harbeck, N., Schmitt, M., et al. (2002). Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Research, 62(3), 840-847.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-6FC2-3
Abstract
Expression analysis of genes encoding components of the phosphotyrosine signaling system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB-453 mammary carcinoma cells, a G to A conversion was discovered that results in the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor. The Arg(388) allele was also found in cell lines derived from a variety of other tumor types as well as in the germ-line of cancer patients and healthy individuals. Analysis of three geographically separated groups indicated that it occurs in approximately 50% of the human population. Investigation of the clinical data of 84 breast cancer patients revealed that homo- or heterozygous carriers of the Arg(338). allele had a significantly reduced disease-free survival time (P = 0.01) within a median follow-up of 62 months. Moreover, the FGFR4 Arg(338) allele was associated with early lymph node metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing FGFR4 Arg(338) exhibited increased motility relative to cells expressing the FGFR4 Gly(338) isotype. Our results support the conclusion that the FGFR4 Arg(338) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression.